tbuckley/cabot-search huggingface dataset:
Abstract 15827: A Case of Ventricular Arrhythmia as Presentation for Cardiac Involvement of Polymyositis
Authors: Jorge Gomez, Carlos Requeña, Amit Mehrotra, Chetan Bhardwaj
Journal: Circulation (2022)

Introduction: Polymyositis is an autoimmune systemic disease which is characterized by chronic weakness and inflammation in skeletal muscle predominantly. Cardiac involvement has been reported and is a poor prognostic factor. Clinical course 61-year-old male with biopsy proven polymyositis with history of cardiac arrest secondary to ventricular fibrillation and dual chamber automatic implantable cardioverter defibrillator (AICD) implanted for secondary prevention. He had recurrent PVC-induced ventricular fibrillation causing AICD shocks. Eventually, he underwent electrophysiology study and successful ablation of PVC targeted to the basal lateral left ventricle.Transthoracic echocardiogram showed unremarkable systolic and akinetic basal inferolateral wall segment.He underwent PET-CT of myocardium which showed focal FDG uptake of the lateral basal left ventricular could indicate focal myocarditis.Endomyocardial biopsy did not show any evidence of myocarditis.Eventually he had recurrent rapid monomorphic ventricular tachycardia and was briefly placed on amiodarone. He was placed on immunosuppressive therapy managed by Rheumatology with etanercept, rituximab and IVIG. No recurrence of ventricular arrythmia has occurred since. Amiodarone has been discontinued. Discussion: Myocardial involvement of polymyositis is not uncommon and has been noted to increase morbidity and mortality.The most common reported manifestations include congestive heart failure, conduction abnormalities which can range from ventricular arrhythmia to complete heart block and coronary artery disease. ConclusionIt is very important to recognize polymyositis as a cause for ventricular arrhythmias in the right clinical setting as management with immunosuppressive therapy can decrease the burden in ventricular arrhythmias.
Abstract 189: Resuscitative Endovascular Balloon Occlusion Of The Aorta In The Obese Patient
Authors: Jacob Broome, Mallory Loe, Lauren Mueller, John Simpson, Danielle Tatum, Sharven Taghavi, PATRICK MCGREW, Olan Jackson-Weaver, Joseph DuBose, juan duchesne
Journal: Circulation (2022)

Objectives: Perceptions of difficulty in obtaining arterial access in obese patients may impact the rate of resuscitative endovascular balloon occlusion of the aorta (REBOA) use in clinical practice. Excess adipose tissue can obstruct palpation of anatomic landmarks, limit sonographic visualization, and potentially increase difficulty of REBOA placement. We aimed to examine the association between obesity and REBOA placement, hypothesizing that increased body habitus would decrease success and increase time to successful aortic occlusion (AO). Methods: A retrospective analysis of the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry was performed on REBOA patients (2013-2022). Patients with systolic blood pressure &gt; 0mmHg admission were included. Patients requiring CPR on arrival to the ED were excluded. Body mass index (BMI) categorized obesity subgroups as follows: non-obese (&lt;30), mildly obese (30-34.9), moderately obese (35-39.9), and severely obese (40+). Results: Inclusion criteria was met by 410 patients. There was no statistical difference in injury severity or admission systolic blood pressure (SBP) among the subgroups. At initiation of AO, moderately and severely obese patients had higher median SBP compared to non- and mildly obese patients (p=0.03). On multivariate analysis, BMI did not significantly impact the success of REBOA placement or time to successful AO. When stratified by arterial access technique, there was no difference in success rates, time to successful AO, or mortality between groups. Overall time to successful AO, response SBP, and mortality did not differ across subgroups. Conclusion: Following traumatic injury in obese patients, REBOA placement is a feasible intervention. Despite differences in patient body habitus, ultrasound guidance was not superior to landmark palpation for acquiring arterial access. Placement of REBOA is equally effective in obese patients and severe obesity should not impede REBOA use.
Abstract 15739: Utility of 30-Day Risk Adjusted Home Time as a Hospital Performance Metric for Transcatheter Edge-to-Edge Mitral Valve Repair
Authors: Amgad Mentias, Milind Y Desai, Neil Keshvani, Saket Girotra, Amar Krishnaswamy, Sameer Hirji, Serge C Harb, Dharam J Kumbhani, Marwan S Saad, Samir R Kapadia, Ambarish Pandey
Journal: Circulation (2022)

Introduction: While the utilization of mitral valve transcatheter edge-to-edge repair (TEER) procedures continues to increase over time, a validated, patient-centered, hospital-level performance metric for TEER is lacking Hypothesis: We examined the utility of 30-risk adjusted home time (HT) as a hospital-level performance metric for TEER procedure and compared it with the established volume, 30-day readmission, and 30-day mortality-based measures. Methods: Medicare patients who received TEER from 2013 to 2019 were identified. HT is defined as time spent alive and out of a hospital, skilled nursing facility, or long-term facility 30 days after TEER. Hospital-level risk-standardized measures of 30-day HT, readmission (RSRR), and mortality (RSMR) were developed using standard risk-adjustment models and correlation between these performance metrics was estimated by Pearson correlation. Longer-term patient-level outcomes of 1-year mortality and readmission were also compared across quartiles of hospitals on 30-day HT. Results: Overall, 24,420 patients who underwent TEER in 344 hospitals were included (mean age 80 y, 54% men, 7% Black race). At the hospital level, the median risk-adjusted 30-day HT was 24 days. There was significant inverse correlation between risk adjusted 30-day HT and 30-day RSRR (r=-0.43), 30-day RSMR (r=-0.5), and modest correlation with hospital’s annual TEER volume (r=0.11, P=0.05). The 1-year readmission and mortality among patients undergoing TEER decreased across increasing 30-day HT categories (Figure). 30-day HT (vs. annual TEER volume) meaningfully reclassified hospital performance in 34% of the hospitals with lower 1-year mortality and readmission among hospitals that were up classified (vs. no change) in performance ranking. Conclusions: Risk-adjusted 30-day HT is a patient-centered, comprehensive quality metric to assess hospital performance in TEER that correlates with important short- and long-term outcomes.
Abstract 15723: Risk Factors for Beta-Blockers Failure in Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Alessandro Trancuccio, Andrea Mazzanti, Deni Kukavica, Gala Giannini, Maira Marino, Luca Casiraghi, Andrea Sugamiele, Patrick Gambelli, Raffaella Bloise, Massimo Morini, Carlo Napolitano, Mirella Memmi, Silvia G Priori
Journal: Circulation (2022)

Introduction: Patients with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) may experience life-threatening arrhythmic events (LAE) despite standard-of-care treatment with beta-blockers (BB), but risk stratification is not well defined. Hypothesis: Both clinical and genetic risk factors predispose to BB failure, including the class of BBs (β1-selective vs. non-selective). Methods: LAE was defined as the composite of sudden cardiac death, aborted cardiac arrest, or hemodynamically non-tolerated ventricular tachycardia. We fitted a Cox proportional hazards regression model with multiple events during BB treatment only with the following explanatory covariates: 1) LAE before diagnosis, 2) unexplained syncope before diagnosis, 3) genotype, and 4) type of BB (as time-dependent variable). Results: We included n=238 CPVT patients: n=135 (57%) probands, n=134 (56%) females, n=216 (91%) RYR2, n=10 (4%) CASQ2, n=5 (2%) RYR2-Loss-of-Function, n=4 (2%) TRDN and n=3 (1%) TECRL. Before the diagnosis, 48/238 (20%) patients experienced an LAE, while 110/238 (46%) patients experienced an unexplained syncope. During a mean follow-up of 9.7±7.6 years of treatment with BB only, 35/238 (15%) patients experienced one or more LAEs (annual rate 4.0%, 95% CI: 3.1%-5.0%), with a mean of 2.1±2.4 LAEs per patient. Multivariable analysis with multiple events at follow-up showed that LAE before diagnosis (HR 3.9; 95%CI: 2.3-6.8; p&lt;0.001), syncope before diagnosis (HR 2.7; 95%CI: 1.5-5.0; p=0.001), TRDN mutations (HR 10.9; 95%CI: 4.2-28.0; p&lt;0.001) and use of β1-selective BBs (HR 3.0; 95%CI: 1.7-5.3; p&lt;0.001) were significantly associated with the occurrence of LAE (Figure). Conclusions: In patients with CPVT, history of LAE and/or unexplained syncope before diagnosis, TRDN mutations and the use of selective BBs are independent risk factors for the occurrence of multiple LAEs at follow-up during BB treatment.
Abstract 15502: Exercise as a Risk Factor for Arrhythmic Mitral Valve Prolapse
Authors: Forrest N Gamble, Kelly E Arps, Sean Pokorney, Albert Sun
Journal: Circulation (2022)

Background: Mitral valve prolapse (MVP) is a common valvular abnormality found in approximately 2.4% of the population. Whereas most cases are benign, an increasingly recognized sequela of MVP is sudden cardiac death (SCD), but risk factors for SCD are not well-defined. Exercise has not been explored as a potential risk factor for SCD in MVP. Hypothesis: We tested the hypothesis that patients with MVP and SCD would be more likely to exercise or be competitive athletes than MVP controls with the capacity to exercise. Methods - The study population was generated from the Duke Epic EHR and determined by ICD-10 codes for MVP and SCD. A comparison group of patients with MVP with exercise data was used. Patients were included if they had guideline-based diagnosis of MVP on echocardiogram or cardiac magnetic resonance imaging. Exercise &lt;1 hour per week was defined as being sedentary and time &gt;1 hour per week or status as a competitive athletes were defined as habitual exercisers. Results: Of the 27 patients with MVP and SCD 18 had documentation of exercise time per week. There were 42 in the control group. Patients with SCD were younger [(54.8 +/-15.1) vs. (63.9 +/- 14.1) p= 0.03], and more likely to have bileaflet prolapse [13/18 (72%) vs. 15/42 (36%), p=0.01]. Patients with SCD were more likely to be habitual exercisers vs. sedentary [16/18 (89%) vs. 17/42 (40.5%), p = .025]. 20 patients with MVP and SCD had documentation of activity level at the time of event. 10 were exercising (50%), 5 (25%) working or doing housework, 4 (20%) resting and 1 (5%) sleeping. Conclusion: Exercise time &gt;1 hour per week is associated with sudden cardiac death in Mitral Valve Prolapse. Exercise may be a trigger of SCD; however, more data is needed to better characterize exercise as a risk factor for SCD in this population.
Abstract 15701: Histone Deacetylase 6Inhibition Demonstrates Comparable Efficacy as Empagliflozin in a Mouse Model of Heart Failure With Preserved Ejection Fraction
Authors: Jin Yang, Aliya Zeng, Sara Vaziri, Iris Wu, Amara Greer-Short, Farshad Farshidfar, Xiaomei Song, Gretchen Argast, Jay Vora, Matt Holdren, Tim Hoey
Journal: Circulation (2022)

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and mortality, yet there are few effective therapies for HFpEF. Previously, we have demonstrated that TN-301, a highly selective small molecule inhibitor of histone deacetylase 6 (HDAC6), works directly on the heart and on systemic metabolism and inflammation in mouse models of HFpEF. Recently, empagliflozin, a selective inhibitor of sodium-glucose transport protein (SGLT2) inhibitor, was approved in the U.S. for patients with HFpEF. Purpose: We aimed to compare the efficacy of HDAC6i and SGLT2i in a mouse model of established diastolic dysfunction with preserved ejection fraction. Methods and Results: To recapitulate systemic and cardiovascular features of HFpEF in humans, we induced diastolic dysfunction with a combination of high fat diet and inhibition of constitutive nitric oxide synthase using N ω -nitrol-arginine methyl ester (L-NAME). After the HFpEF phenotypes were established, mice received TYA-11018 (TN-301-like HDAC6i) or empagliflozin, or vehicle orally once daily for 9 weeks. We found that TYA-11018 reduced left ventricular hypertrophy and restored diastolic function with comparable efficacy to empagliflozin. In addition, TYA-11018 reduced fasting glucose and improved glucose tolerance in HFpEF mice, to levels similar to empagliflozin. Preliminary data suggested TYA-11018 corrects hyperglycemia independently of glucose urine excretion, which is distinct from SGLT2i. Using whole transriptome RNA-seq, TYA-11018 showed greater effects on correcting expression of gene sets associated with inflammation, fibrosis and mitochondrial energy production compared to empagliflozin in HFpEF hearts. Conclusion: Our results show that with its distinct HDAC6 inhibition mechanism, TYA-11018 reverses preexisting hypertrophy, diastolic dysfunction and glucose tolerance, demonstrated similar efficacy to that with a SGLT2 inhibitor in HFpEF model. The comparable efficacy seen in this HFpEF model with TYA-11018 and empagliflozin provides early but encouraging evidence of the potential translatability of these findings to clinical development. We are developing TN-301 for treating HFpEF patients.
Abstract 15591: Acute Dantrolene Treatment Reverses Arrhythmogenic Substrate and Reduces Triggers Induced by Ryanodine Receptor 2 Hyperactivity in Human Hearts
Authors: Sharon Ann George, Igor R Efimov
Journal: Circulation (2022)

Introduction: Ryanodine receptor 2 (RyR2) hyperactivity is commonly observed in structural heart diseases that are a result of ischemia or heart failure. It results in abnormal calcium handling and calcium leak that can trigger arrhythmias. Dantrolene, a RyR inhibitor, is used to prevent calcium leak from RyR1 in skeletal muscles. Hypothesis: Suppressing RyR2 hyperactivity with acute dantrolene treatment can reduce arrhythmia burden in human hearts. Methods: Human donor hearts that were not used in transplantation were obtained and 1 cm 3 cubes were isolated from the left ventricle. Slices at 400 μm thickness were generated from these cubes, pinned and perfused with Tyrode’s solution in a recording tissue chamber. Pseudo-ECGs were recorded with ECG electrodes and the slices were optically mapped to measure conduction velocity (CV), action potential duration (APD) and calcium transient duration (CaTD). After an initial 30 min equilibration period, baseline optical recordings were obtained. Slices were then treated with 1) Isoproterenol (Iso, 250 nM) to stimulate β-adrenergic receptors, 2) Caffeine (200 μM) for RyR2 receptor activation and 3) Dantrolene (10 μM), sequentially. Dual optical recordings, Vm and Ca, were obtained after each treatment. Results: Substrate: Iso reduced APD (425±36 vs 394±43, p=0.03), as expected, and addition of Caffeine restored APD to baseline. More importantly, addition of Dantrolene prolonged APD even further (460±90, p=0.04). CaTD was also similarly reduced by Iso (445±48 vs 387±25, p=0.04) and restored to baseline by Caffeine+Iso. No significant changes in CV were measured under any condition. Trigger: In slices where PVCs were inducible, Caffeine+Iso increased occurrence of PVCs (20 vs 53 PVCs/min) while addition of Dantrolene reduced PVC incidence (18 PVCs/min). Conclusions: Dantrolene treatment, acutely reversed proarrhythmogenic substrate and reduced triggers and could therefore be a suitable approach for anti-arrhythmic therapy in patients with structural heart disease. Additionally, human LV slice preparation is useful in antiarrhythmic drug studies.
Abstract 15628: Incidence, Complications, and Outcomes of Non - ST Elevation Myocardial Infarction in Patients Presenting With Acute Ischemic Stroke
Authors: Shivani Mehta
Journal: Circulation (2022)

Background: Acute myocardial infarction may concomitantly occur with acute ischemic stroke. The incidence,complications and outcomes of acute Non- ST elevation Myocardial infarction in acute ischemic stroke are not well studied. Methods: We examined hospitalized patients (n = 1,726,265) with acute ischemic stroke that were included in National Inpatient Sample 2016-2019. Acute ischemic stroke and NSTEMI were defined by using International classification of disease (ICD -10). STEMI patients were excluded. Multivariable logistic regression analysis was used to examine association of NSTEMI with outcomes. A subgroup analysis of NSTEMI patients that underwent PCI (with or without angioplasty) was also performed. Results: Of the total stroke patients, 27630 (1.6%) patients (mean age 73.5, 52.2% females) had NSTEMI diagnosed during the hospitalization. Of these, 3890 (6.32%) died in NSTEMI group and 57670 (93.68%) died in non NSTEMI group. The commonest complications in NSTEMI group were cardiogenic shock 25% , cardiac tamponade 13.8% , and septic shock 12.1%. NSTEMI in stroke patients were associated with several complications and mortality (OR 2.73, 95% CI 2.57-2.90, p value &lt;0.001). While, PCI was performed in 43.3% of NSTEMI patients, there was no increase in bleeding complications and there was reduced risk of mortality associated with PCI (OR 0.34, 95% CI 0.22-0.52, p&lt;0.001)[FIGURE]. Conclusion: NSTEMI even though not frequent in patients with stroke but was associated with increased risk of complications and mortality. PCI was associated with reduced risk of mortality and no increase in bleeding complications.
Abstract 15501: Rare Genomic Copy Number Variants Implicate New Candidate Genes for Bicuspid Aortic Valve
Authors: Steven G Carlisle, Hasan Albasha, Hector I Michelena, Anna Sabate-Rotes, Lisa Bianco, Julie DeBacker, Laura Muino Mosquera, Angela T Yetman, Malenka Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn Hui, Anthony D Caffarelli, Yuli Y Kim, Dongchuan Guo, Rodolfo Citro, Margot De Marco, Justin Tretter, Neil A Hanchard, John W Belmont, Kim L McBride, Simon C Body, Siddharth K Prakash
Journal: Circulation (2022)

Introduction: Bicuspid Aortic Valve (BAV), the most common adult congenital heart defect, is a major cause of aortic insufficiency or stenosis requiring valve replacement and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications to sporadic late onset disease. We determined the frequency and gene content of rare genomic copy number variants (CNVs) in isolated BAV cases. Methods: We performed genome-wide SNP microarray analysis of familial BAV cases with early onset complications in the UTHealth BAV Research Registry (EBAV, n=394) and elderly probands from the International BAV Consortium (BAVCON, n=4216). CNVs were detected in Illumina genotypes using the PennCNV, QuantiSNP and cnvPartition algorithms. BAV cases were compared to 16,576 controls without known cardiovascular disease from the Database of Genotypes and Phenotypes. Only CNV calls with &gt;6 consecutive variants, &gt;20 kb in length, identified by at least two algorithms and intersected with known genes were included. For comparison, we assessed a cohort with left ventricular outflow tract obstructive lesions including BAV (LVOTO, n=1561) using identical methods. CNV burden and associations were tested using PLINK. Results: We identified 84 large recurrent CNVs in BAV cases that are absent or rare (&lt;0.1%) in controls. 34 rare CNVs overlap between BAV and LVOTO cases and involve candidate genes that interact with each other during heart development. The largest and most prevalent of the recurrent CNVs are 8p23 duplications involving GATA4 (OR 340, CI: 42-2700). CNVs of genes that cause BAV when mutated were significantly enriched in cases (n=135, P =1x10 -27 ). The overall burden of rare genic CNVs, specifically large deletions, was also increased in BAV cases (empiric P &lt; 1x10 -5 ) and was higher in younger EBAV cases than in older BAVCON cases. Conclusion: We identified likely pathogenic CNVs in more than 10% of BAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV.
Abstract 15638: Proinflammatory and Proangiogenic State Promotes Malignant Melanoma Progression in Mouse Model of HFpEF
Authors: Liwei Lang, Vadym Buncha, Zsolt A Bagi
Journal: Circulation (2022)

Epidemiological studies have shown that the incidence of various cancers, such as malignant melanoma is higher in patients with heart failure (both HFrEF and HFpEF) than in age-matched population, but the underlying mechanisms remain unknown. We hypothesized that in HFpEF a chronic systemic inflammation promotes malignant melanoma progression. To test this hypothesis orthotopic melanoma xenograft model was employed in a mouse model of HFpEF. Mice with uninephrectomy, aldosterone infusion (UNX-Aldo) with osmotic minipump (Alzet, 0.30 μg/h), and high salt ingestion (1% in drinking water) develop left ventricle diastolic dysfunction as indicated by a significantly (p&lt;0.05) reduced E/A ratio (E=early, A=late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time and E wave deceleration time, with no change in the ejection fraction. Mouse melanoma B16F10 cells labelled with firefly luciferase was injected in the mouse ear of UNX-Aldo and control mice. Using in vivo bioluminescence imaging we found a significantly augmented tumor growths in the UNX-Aldo mice. UNX-Aldo mice display a robust increase in several serum inflammatory mediators, cytokines and chemokines, such as IL-1, IL-6, TNF, IFN-γ, MCP-1, CD14, CCL12, CXCL13/16, as well as decreases in anti-inflammatory cytokines, such as IL-10, as measured in a Proteome Profiler cytokine array. In addition, UNX-Aldo mice had increased level of multiple angiogenic growth factors, such as IGFBP-1 and GM-CSF. Flow cytometry analysis also revealed and elevated number of tumor-associated, CD11b+F480-Ly6G+CXCL1+ neutrophils in the grafted tumors in UNX-Aldo mice. Collectively, our results indicate that pro-inflammatory and proangiogenic state in experimental HFpEF exacerbates melanoma tumor growth.